This application is for the Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) clinical center at Saint Louis University. The NASH Clinical Research Network (NASH CRN) has been sponsored by the NIDDK since 2002 with a renewal in 2009. Nonalcoholic fatty liver disease (NAFLD) affects one out of three adults and one in five children in North America and is thus an emerging public health issue in the United States. NAFLD, and especially nonalcoholic steatohepatitis (NASH), may lead to cirrhosis and primary liver cancer resulting in death or liver transplant thus leading to major increases in health burdens and costs. The NASH CRN is ideally and uniquely positioned to impact the growing public health significance of NASH that can only be addressed via a large research consortium. The primary objective of the NASH CRN is to perform clinical trials of therapeutic agents for NASH and NAFLD in adults and children. A closely linked and high priority secondary objective is to conduct translational research in NASH and NAFLD focusing on the pathogenesis that will provide the basis for understanding the natural history and developing means of better diagnosis, prevention, treatment, and clinical management. In the next phase of the NASH CRN, the adult and pediatric therapeutic trials initiated during the previous funding cycle will be completed and new therapeutic trials, including phase 2a proof of mechanism and phase 2b clinical trials will be initiated to develop evidence-based treatment options that are safe, effective, simple, and inexpensive. The longitudinal cohort of adults and children with NAFLD collected over the past decade will be extended to prospectively define the natural history of the disease, the cardiovascular and metabolic risk factors, and will aid in biomarker discovery and validation. This cohort will also facilitate the development and validation of non-invasive techniques to identify those with NASH/NAFLD, predict who will respond to treatments, and identify factors affecting disease progression. The NASH CRN is poised to continue its major impact on the field and directly advance the mission of the National Institutes of Health to improve the health of the public.